Jane March

My research aims to improve the early detection of ovarian cancer by uncovering the molecular features of its clinically relevant biomarker CA125. While CA125 levels are widely used to monitor disease progression and recurrence, surprisingly little is known about the protein’s full molecular structure and how clinical affinity agents recognize it in patient samples. A deeper molecular understanding of CA125 is critical for improving diagnostic accuracy, particularly for early-stage ovarian cancer cases and for patient populations whose CA125 variants are underrepresented in current testing. 

Existing literature focuses on a small region of CA125 known as the tandem repeat domain, as this is the region targeted by the clinically used assay. However, this domain comprises less than 15% of the full protein, and the antibodies used in the assay do not recognize it uniformly, which contributes to false-negative test results (i.e. the test says no cancer is present when really it is). My work moves beyond this limited view of CA125. Using a combination of mutagenesis, immunoassay development, and glycoproteomic mass spectrometry, I investigate how CA125 structure and post-translational modifications (such as glycosylation) vary across patient groups. By taking a holistic, molecule-wide approach, my research seeks to identify the sources of CA125 heterogeneity and enable the development of improved, affinity-free reagents for ovarian cancer detection.